There is substantial and growing data suggesting that disruption of the normal, healthy gastrointestinal (GI) tract microbial environment (the GI microbiome), which consists of a wide variety of GI organisms (GI microflora), can play a critical role in the development of a wide variety of diseases affecting populations throughout the world. As such, there have been increasing efforts to develop strategies to restore imbalances in GI microflora. Such strategies include probiotics, and a process known as fecal microbiota transplantation (FMT) (also called “intestinal microflora transplantation”, “fecal biotherapy”, “fecal biotransplant”, “fecal bacteriotherapy”, “fecal flora reconstitution”, “stool transplantation”, or “fecal transplantation”), the latter of which seems to overcome all of the many disadvantages of the former. While, for purposes of clarity the term “FMT” or “fecal biotherapy” will be used for the remainder of this disclosure, the current inventors propose that this therapy be renamed “Gastrointestinal Floral Transplantation (GIFT)”.
In sum, FMT involves the administration of a fully comprehensive composition or endogenous human GI microflora taken from a healthy (as determined by pre-treatment screening for stool and blood borne pathogens) donor's stool and delivered (transplanted) directly into the lower GI tract of an affected individual to reconstitute their disrupted microfloral environment. This strategy can overcome many of the limitations of oral probiotics, the commonly used, yet relatively ineffective strategy used to modify the GI microflora. First, unlike probiotics (the composition of which generally represent only 0.01% of roughly 100 trillion organisms in the normal GI microbiome), the microflora composition used in FMT approximates 100% of the normal GI microflora composition. Second, through various methods (most commonly colonoscopy, enema, or nasoenteric tube), nearly 100% of the microflora may be delivered in biologically active state directly to the target location of the GI tract, bypassing the hazards encountered through oral administration of probiotics, where only a fraction can survive. Third, unlike probiotics, most if not all of the microorganisms in FMT may be endogenous, have co-evolved, and may be fully adapted to the GI milieu to which they are delivered, and thus are typically able to survive after transplantation. Lastly, in contrast to nonspecifically mass produced probiotics, FMT can allow for selection of stool donors who are either related to and/or live with the affected individual, and thus whose GI microflora compositions have been similarly determined either genetically and/or environmentally, increasing the probability that the transplanted microflora composition will resemble that of the recipient's.
However, despite FMT's therapeutic potential in many highly prevalent and disabling conditions, including, but not limited to the epidemic of Clostridium Difficile infection (C. difficile, C. diff, or CDI), where it consistently demonstrates over a 90% cure rate in recurrent cases, a number of disadvantages in current therapeutic methods may serve to prevent its adoption in the vast majority of practice.
The general necessary sequential processes for executing FMT are as follows: First, collection of donated stool is accomplished through a requisite step of manually transferring donated stool from either the toilet bowl, freestanding commode, or other simple collection apparatus (such as a rigid plastic bowl or bag placed within the toilet) into another container. In many cases, the stool is weighed to ensure a specific and adequate amount of stool is available for processing. Excess stool is transferred into another container and disposed of. The weighed stool is transferred into a household blender or food processor. Diluents such as saline, 4% milk, or other such diluents are manually added to the mixing apparatus, and the stool is homogenized into a slurry consistency. This homogenized stool is then filtered (e.g. through a simple funnel covered with a coffee or urine stone strainer, or gauze pads) into another container, such as an enema bag, for example. Finally, the filtered liquid stool is crudely transferred from this tertiary or quaternary container into various devices such as a colonoscope (with the use of a syringe), enema kit, or nasoenteric tube for delivery to the patient. Of note, stool is a level 2 biohazard, and it is recommended that those involved in any of the aforementioned processes use universal precautions (gown, gloves, mask and eye protection), and that said processes be conducted under a laboratory hood once stool has been collected. All reusable items may then be sterilized in an autoclave or through other means, and non-reusable items disposed of. Taken together, there are many limitations to performing FMT: the process is quite unappealing (i.e. “gross”) to providers, patients and donors, carries significant risks of insanitation (for the user and environment) and contamination (of the stool sample and microflora), has highly unappealing aesthetics, and is burdensomely inefficient with regards to carrying out the sequential processes. There is also no simple or standardized protocol, ensuring reliably repeatable formulations are produced. Further, it can be desirable to advance methods of fecal biotherapy so that it can delivered through more diverse and appealing processes, where the microflora must be significantly refined and isolated for potential incorporation into modes of delivery such as capsules, foods, or liquids for oral consumption. Under the current methodology, such modes of delivery are neither practical nor appealing.
Because there have been no technological innovations developed to specifically or comprehensively address the sequential processes required for FMT, the following resultant overarching limitations have dramatically discouraged the adoption of this highly effective therapy in the vast majority of practice:
Risk of Insanitation (for the user and environment) and Contamination (of the stool sample and microflora): Because the prior art requires that stool is collected, transferred, processed, and cleaned in a largely “open-system”, where the user and environment are repeatedly exposed to the stool and vice versa, there is significant risk of insanitation (for the user and environment) and contamination (of the stool sample), respectively.
Unappealing Aesthetics (of performing necessary sequential processes): While the general concept of this therapy alone is inherently unappealing to all parties involved, it is also somatically abrasive throughout the entire sequence of processes, as the stool is visible, and the stool's malodor is unmitigated. Further, and with respect to further limitations described below, without effective methods to refine and aesthetically improve microflora from stool, it will not be possible to advance delivery methods for FMT where the target component (microflora) can be delivered through other mechanism where visible appearance, taste, smell, and/or potency (or concentration) are salient features.
Inefficiency (of performing necessary sequential processes): As a result of the numerous necessary separate sequential collection and preparation steps, the various required apparatuses, the subsequent need to clean said apparatuses, and the required protective gear and dedicated space to carry out said preparation and cleaning, the overall process of executing FMT may be quite inefficient. Such inefficiency may not only problematic as it can relate to the previous two major aforementioned limitations above, but also because in practice it may often be impractical and time consuming for the various users involved.
Indeed, in considering the relevance of described prior art to the aforementioned limitations of FMT, it can seem that such current methodologies can offer only partial mitigation of some aspects relating to the risk of insanitation and contamination, and unappealing aesthetics (such as can be provided through various stool collection devices), while failing to significantly address the limitation of inefficiency all together. Further, to the extent that current methodologies can mitigate the limitations of risk of insanitation and contamination, and unappealing aesthetics, said mitigation may address only the collection process, and may not address these limitations within the requisite subsequent steps involved in FMT—processing the stool, isolating the microflora, and delivering the microflora to the patient.
While various innovations in stool collection devices have been designed to mitigate certain undesirable limitations of stool collection, generally for the purpose of improving the process of collecting and preserving donated stool samples for subsequent analysis (such as diagnostic tests), none are adapted for the unique needs of FMT, or advancements thereof. Certain innovations in stool collection devices have attempted to further decrease unwanted contamination of stool by urine, improve transportation function, and allay some unappealing aesthetic aspects of stool odor and visualization after stool donation (U.S. Pat. No. 6,351,857 and U.S. Publication 2008/0108961). There have also been a wide variety of devices and methods developed for the purpose of processing stool samples, again typically for the purposes of subjecting the stool sample to a diagnostic test. The stool collection device is generally separate from the stool processing device, and thus necessitates transfer of the stool from the former to the latter. There has been an attempt to incorporate a processing mechanism directly within a disposable in-toilet stool collection device designed with built-in motor-driven blades, and the ability to infuse fluid through ports for stool homogenization, as well as a valve outlet for dispensation (U.S. Pat. No. 4,101,279). However, while intended to offer certain conveniences in stool collection and processing, this stool collection device was, similar to the vast majority of other stool collection devices, intended to aid subsequent diagnostic applications, and had no proposed applications for FMT. As such, it can have many shortcomings with respect to effectively performing and advancing FMT, if one were to propose such an adapted application. The stool collection device generally lacks any method for refining the stool, microflora, or filtrates thereof in any way. Additionally, while it may the capacity to crudely transfer contents from within the container through a conduit, it is not designed specifically to offer any method of delivering FMT efficiently to a recipient's colon either directly or indirectly within a closed system. It also would seem that in the principal described embodiment with a conventional metal blender blade, this device not only can have the significant potential to place the stool donor at risk of injury, but may be limited in scope with respect to modes of performing homogenization and stool processing. This device may also not be designed to accommodate varied amounts of stool and diluents, where fixed ratios may require large volumes of substance be sealed within the container. Where condensing the size of the device may be reliable for storage or shipping of contents, the device seems to lack any mechanism for reducing its size, or adapting its conformation.
It is thus desirable to provide a device that overcomes the aforementioned limitations by allowing for the necessary sequential processes of FMT (i.e. direct stool collection, liquification and homogenization, comprehensive microflora isolation and refinement, and microflora delivery to recipient) to be performed in an efficient and sanitary manner within a closed system, and that offers mechanism of advancing delivery methods of FMT.